The FDA released briefing documents for two products on the slate for consideration at Thursday's meeting of the dermatologic and ophthalmologic drugs advisory committee.

Lucentis, a product of Genentech Inc., of South San Francisco, will be considered for approval for diabetic macular edema, and Jetrea (ocriplasmin intravitreal injection), by ThromboGenics Inc., of Iselin, N.J., is proposed for symptomatic vitreomacular adhesion.

Lucentis already is approved for wet, age-related macular degeneration, but would be the first intravitreally administered drug approved for diabetic macular edema.

According to Genentech, about 25.8 million Americans, or 8.3 percent of the population, have diabetes, and are vulnerable to diabetic macular edema as the disease slowly damages the blood vessels of the eye. About 4.2 million Americans older than 40 have diabetic retinopathy. The current standard of care is surgery.

Lucentis is believed to decrease retinal edema by decreasing retinal capillary permeability. Genentech, a member of the Roche Group, provided two Phase III studies to support the safety and efficacy of Lucentis in that indication. Each of the double-masked, randomized, sham-injection-controlled studies collected data on the two groups for 24 months before giving the sham group the option to cross over and receive Lucentis instead for the next 12 months.

About 122 subjects received 0.5 mg Lucentis injection, 122 received 0.3 mg Lucentis injection and 122 received sham injection. Each patient received an injection in one eye, the study eye, only. The other eye was treated with laser photocoagulation, which is the standard of care.

The study had as its primary endpoint a gain of at least 15 letters of vision from baseline at 24 months. Genentech reported that a significantly greater number of patients who received Lucentis were able to read at least 15 more letters on the eye chart than they could at the beginning.

In the 0.3 mg group, 39.2 percent achieved that benchmark. For the 0.5 mg group, it was 42.5 percent, and 15.2 percent for the sham injection control group.

Genentech found that Lucentis was generally well tolerated in patients with DME, and its safety profile was similar to that already established in the wet AMD indication.

Questions the advisory committee will be considering include whether there is a significant difference in efficacy between the 0.3 mg and 0.5 mg group, whether evidence supports the efficacy of Lucentis for diabetic macular edema, whether additional studies may be needed, and any concerns about labeling.

Adverse events in the trial included a greater incidence of strokes in patients treated with 0.5 mg Lucentis compared with the control group (but not the 0.3 mg Lucentis group). There was also a greater incidence of death in patients treated with Lucentis. Seven patients (2.8 percent) died in the 0.3 mg group, 11 patients (4.4 percent) died in the 0.3 mg group and only three (1 .2 percent) died in the sham injection group.

There were also greater incidences of hypertension and wound healing complications associated with Lucentis.

Jefferies analyst Biren Amin said that the briefing docs were in line with expectations and that a positive recommendation seemed likely. "We expect a positive recommendation for Lucentis, at least for the 0.3 mg dose with 0.5 mg vulnerable on higher safety risks without incremental efficacy benefit," wrote Amin.

That is good news for Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., because it is likely to be able to achieve similar results in diabetic macular edema with Eylea. "We believe REGN should modify its ongoing U.S. Eylea PIII VISTA to satisfy FDA by incorporating percent of patients with greater than or equal to a 15-letter gain as the primary endpoint," Amin wrote.

Ocriplasmin Under the Microscope

Ocriplasmin goes up before the committee the afternoon of July 26. It also has two Phase III, randomized, placebo-controlled, double-masked studies supporting its approval. The objective of the two identically designed trials was to evaluate safety and efficacy of a single intravitreal injection of 125 mcg ocriplasmin in subjects with focal vitreomacular adhesion; 326 subjects were enrolled in each study.

For the primary endpoint of resolution of VMA at day 28, there was a statistically significant treatment effect. A majority of treated patients achieved that goal by day seven, with maintenance through the end of the six-month follow-up period. Thrombogenics also reported positive results for secondary endpoints.

Ocriplasmin is a recombinant human plasmin. It would be the first pharmacologic treatment for the condition, which is currently only treatable with surgery. Vague questions in the documents sent Thrombogenics stock (EN Brussels:THR) down 6.43 percent.

The advisory committee will discuss whether the drug is safe and effective for vitreomacular adhesions, macular holes associated with vitreomacular adhesions and all macular holes regardless of the presence of adhesions. It will also discuss the possible need for additional studies, the benefits vs. risks of the drug and any potential labeling concerns.

Phillippa Gardner, of Jefferies, called the questions "rather generic," and said that it is difficult to "get a steer on the FDA's thoughts." According to Gardner, approval is expected in line with the positive panel endorsement.